Terbium-Labeled Gold Nanoparticles as Nanoscale Brachytherapy Agents Against Breast Cancer.

Due to their intriguing emission profile, Terbium-161 (Tb) radiopharmaceuticals seem to bring significant advancement in theranostic applications to cancer treatment. The combination of Tb with nanoscale brachytherapy as an approach for cancer treatment is particularly advantageous and promising. Herein, we propose the application of a hybrid nanosystem comprising gold decorated (Au@TADOTAGA) iron oxide nanoflowers as a form of injectable nanobrachytherapy for the local treatment of breast cancer.

Increase of OH radical yields due to the decomposition of hydrogen peroxide by gold nanoparticles under X-ray irradiation.

We elucidate the decomposition mechanism of hydrogen peroxide, which is formed by water radiolysis, by gold nanoparticles (GNPs) under X-ray irradiation. The variations in yields of hydrogen peroxide generated in the presence of GNPs are evaluated using the Ghormley technique. The increase of yields of OH radicals has been quantified using Ampliflu® Red solutions.

Quantitative, precise and multi-wavelength evaluation of the light-to-heat conversion efficiency for nanoparticular photothermal agents with calibrated photoacoustic spectroscopy.

Biomedical photothermal therapy with optical nanoparticles is based on the conversion of optical energy into heat through three steps: optical absorption, thermal conversion of the absorbed energy and heat transfer to the surrounding medium. The light-to-heat conversion efficiency (LHCE) has become one of the main metrics to quantitatively characterize the last two steps and evaluate the merit of nanoparticules for photothermal therapy. The estimation of the LHCE is mostly performed by monitoring the temperature evolution of a solution under laser irradiation.

Evaluation of Radiosensitization and Cytokine Modulation by Differentially PEGylated Gold Nanoparticles in Glioblastoma Cells.

Glioblastoma (GBM) is known as the most aggressive type of malignant brain tumour, with an extremely poor prognosis of approximately 12 months following standard-of-care treatment with surgical resection, radiotherapy (RT), and temozolomide treatment. Novel RT-drug combinations are urgently needed to improve patient outcomes. Gold nanoparticles (GNPs) have demonstrated significant preclinical potential as radiosensitizers due to their unique physicochemical properties and their ability to pass the blood-brain barrier.

Radiosensitization with Gadolinium Chelate-Coated Gold Nanoparticles Prevents Aggressiveness and Invasiveness in Glioblastoma.

Purpose: This study aimed to evaluate the radiosensitizing potential of Au@DTDTPA(Gd) nanoparticles when combined with conventional external X-ray irradiation (RT) to treat GBM.

Methods: Complementary biological models based on U87 spheroids including conventional 3D invasion assay, organotypic brain slice cultures, chronic cranial window model were implemented to investigate the impact of RT treatments (10 Gy single dose; 5×2 Gy or 2×5 Gy) combined with Au@DTDTPA(Gd) nanoparticles on tumor progression. The main tumor mass and its infiltrative area were analyzed.

Quantitative Comparison of the Light-to-Heat Conversion Efficiency in Nanomaterials Suitable for Photothermal Therapy.

Functional colloidal nanoparticles capable of converting between various energy types are finding an increasing number of applications. One of the relevant examples concerns light-to-heat-converting colloidal nanoparticles that may be useful for localized photothermal therapy of cancers. Unfortunately, quantitative comparison and ranking of nanoheaters are not straightforward as materials of different compositions and structures have different photophysical and chemical properties and may interact differently with the biological environment.

Two step promotion of a hot tumor immune environment by gold decorated iron oxide nanoflowers and light-triggered mild hyperthermia.

Nanoparticle-mediated photothermal therapy (PTT) is an emerging modality to treat tumors with both spatial and temporal control provided by light activation. Gold decorated iron oxide nanoflowers (GIONF) are good candidates for PTT due to their biocompatibility, biodegradability and light-to-heat conversion. Profound changes in the tumor immune environment might be early induced by the gold and iron oxide metallic agents in addition to the photothermal effects.

Characterization and biodistribution of Au nanoparticles loaded in PLGA nanocarriers using an original encapsulation process.

Due to their imaging and radiosensitizing properties, ultrasmall gadolinium chelate-coated gold nanoparticles (AuNP) represent a promising approach in the diagnosis and the treatment of tumors. However, their poor pharmacokinetic profile, especially their rapid renal clearance prevents from an efficient exploitation of their potential for medical applications. The present study focuses on a strategy which resides in the encapsulation of AuNP in large polymeric NP to avoid the glomerular filtration and then to prolong the vascular residence time.

The detrimental invasiveness of glioma cells controlled by gadolinium chelate-coated gold nanoparticles.

Glioblastoma are characterized by an invasive phenotype, which is thought to be responsible for recurrences and the short overall survival of patients. In the last decade, the promising potential of ultrasmall gadolinium chelate-coated gold nanoparticles (namely Au@DTDTPA(Gd)) was evidenced for image-guided radiotherapy in brain tumors. Considering the threat posed by invasiveness properties of glioma cells, we were interested in further investigating the biological effects of Au@DTDTPA(Gd) by examining their impact on GBM cell migration and invasion.

Photothermal Depletion of Cancer-Associated Fibroblasts Normalizes Tumor Stiffness in Desmoplastic Cholangiocarcinoma.

Physical oncology recognizes tissue stiffness mediated by activation of cancer-associated fibroblasts (CAF) and extracellular matrix remodeling as an active modulator of tumorigenesis, treatment resistance, and clinical outcome. Cholangiocarcinoma (CCA) is a highly aggressive and chemoresistant desmoplastic cancer enriched in CAF. CCA's stroma mechanical properties are considered responsible for its chemoresistant character.

A Proof-of-Concept Study on the Therapeutic Potential of Au Nanoparticles Radiolabeled with the Alpha-Emitter Actinium-225.

Actinium-225 (Ac) is receiving increased attention for its application in targeted radionuclide therapy, due to the short range of its emitted alpha particles in conjunction with their high linear energy transfer, which lead to the eradication of tumor cells while sparing neighboring healthy tissue. The objective of our study was the evaluation of a gold nanoparticle radiolabeled with Ac as an injectable radiopharmaceutical form of brachytherapy for local radiation treatment of cancer. Au@TADOTAGA was radiolabeled with Ac at pH 5.

Uptake and excretion dynamics of gold nanoparticles in cancer cells and fibroblasts.

Radiotherapy is one of the main treatments used to fight cancer. A major limitation of this modality is the lack of selectivity between cancerous and healthy tissues. One of the most promising strategies proposed in this last decade is the addition of nanoparticles with high-atomic number to enhance radiation effects in tumors.

Fluorescent Radiosensitizing Gold Nanoparticles.

Ultrasmall polyaminocarboxylate-coated gold nanoparticles (NPs), Au@DTDTPA and Au@TADOTAGA, that have been recently developed exhibit a promising potential for image-guided radiotherapy. In order to render the radiosensitizing effect of these gold nanoparticles even more efficient, the study of their localization in cells is required to better understand the relation between the radiosensitizing properties of the agents and their localization in cells and in tumors. To achieve this goal, post-functionalization of Au@DTDTPA nanoparticles by near-infrared (NIF) organic dyes (aminated derivative of cyanine 5, Cy5-NH) was performed.

Quality control of gold nanoparticles as pharmaceutical ingredients.

Nanoparticles are being developed for a wide range of medical applications such as, controlled release, drug delivery systems or imagery, theranostics, implants…. For the moment, there is no legal definition of nanoparticles or nanomaterials for therapeutic use. The specific case of gold nanoparticles is not an exception: their current definition as nanoparticle material does not correspond to classic pharmaceutical ingredients as described in Pharmacopoeias.

The contribution of hydrogen peroxide to the radiosensitizing effect of gold nanoparticles.

Plasmid DNA in aerated aqueous solution is used as a probe to determine whose of the reactive oxygen species (ROS) generated after absorption of ultra-soft X-rays (USX) take part in biomolecule damage in the presence and in absence of Gold Nano-Particles (GNP) and specific scavengers. Citrate-coated GNPs with core sizes of 6, 10 and 25 nm are synthetized and characterized, especially in terms of plasmon band shift, ζ-potential and hydrodynamic radii (respectively 9, 21 and 30 nm). We confirm the radiosensitizing effect of GNP and show that the SSB number per plasmid increases when, for a same mass of gold element, the core size of the gold nanoparticles decreases.

Preclinical evaluation of gold-DTDTPA nanoparticles as theranostic agents in prostate cancer radiotherapy.

Aim: Gold nanoparticles have attracted significant interest in cancer diagnosis and treatment. Herein, we evaluated the theranostic potential of dithiolated diethylenetriamine pentaacetic acid (DTDTPA) conjugated AuNPs (Au@DTDTPA) for CT-contrast enhancement and radiosensitization in prostate cancer.

Materials & Methods: In vitro assays determined Au@DTDTPA uptake, cytotoxicity, radiosensitizing potential and DNA damage profiles.

Enhanced chemiluminescence-based detection on gold substrate after electrografting of diazonium precursor-coated gold nanoparticles.

Since it was demonstrated that nanostructured surfaces are more efficient for the detection based on the specific capture of analytes, there is a real need to develop strategies for grafting nanoparticles onto flat surfaces. Among the different routes for the functionalization of a surface, the reduction of diazonium salts appears very attractive for the covalent immobilization of nanoparticles because this method does not require a pre-treatment of the surface. For achieving this goal, gold nanoparticles coated by precursor of diazonium salts were synthesized by reduction of gold salt in presence of mercaptoaniline.

Thermodynamic stability and kinetic inertness of a Gd-DTPA bisamide complex grafted onto gold nanoparticles.

Gold nanoparticles coated by gadolinium (III) chelates (Au@DTDTPA) where DTDTPA is a dithiolated bisamide derivative of diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA), constituted contrast agents for both X-ray computed tomography and magnetic resonance imaging. In an MRI context, highly stable Gd(3+) complexes are needed for in vivo applications. Thus, knowledge of the thermodynamic stability and kinetic inertness of these chelates, when grafted onto gold nanoparticles, is crucial since bisamide DTPA chelates are usually less suited for Gd(3+) coordination than DTPA.

Biodegradation mechanisms of iron oxide monocrystalline nanoflowers and tunable shield effect of gold coating.

Understanding the relation between the structure and the reactivity of nanomaterials in the organism is a crucial step towards efficient and safe biomedical applications. The multi-scale approach reported here, allows following the magnetic and structural transformations of multicore maghemite nanoflowers in a medium mimicking intracellular lysosomal environment. By confronting atomic-scale and macroscopic information on the biodegradation of these complex nanostuctures, we can unravel the mechanisms involved in the critical alterations of their hyperthermic power and their Magnetic Resonance imaging T1 and T2 contrast effect.

The In Vivo Radiosensitizing Effect of Gold Nanoparticles Based MRI Contrast Agents.

Owing to the high atomic number (Z) of gold element, the gold nanoparticles appear as very promising radiosensitizing agents. This character can be exploited for improving the selectivity of radiotherapy. However, such an improvement is possible only if irradiation is performed when the gold content is high in the tumor and low in the surrounding healthy tissue.

The in vivo radiosensitizing effect of gold nanoparticles based MRI contrast agents.

Owing to the high atomic number (Z) of gold element, the gold nanoparticles appear as very promising radiosensitizing agents. This character can be exploited for improving the selectivity of radiotherapy. However, such an improvement is possible only if irradiation is performed when the gold content is high in the tumor and low in the surrounding healthy tissue.

The biodistribution of gold nanoparticles designed for renal clearance.

Owing to their tunable optical properties and their high absorption cross-section of X- and γ-ray, gold nanostructures appear as promising agents for remotely controlled therapy. Since the efficiency of cancer therapy is not limited to the eradication of the tumour but rests also on the sparing of healthy tissue, a biodistribution study is required in order to determine whether the behaviour of the nanoparticles after intravenous injection is safe (no accumulation in healthy tissue, no uptake by phagocytic cell-rich organs (liver, spleen) and renal clearance). The biodistribution of Au@DTDTPA nanoparticles which are composed of a gold core and a DTDTPA (dithiolated polyaminocarboxylate) shell can be established by X-ray imaging (owing to the X-ray absorption of the gold core) and by magnetic resonance imaging (MRI) since the DTDTPA shell was designed for the immobilization of paramagnetic gadolinium ions.

Cooperative organization in iron oxide multi-core nanoparticles potentiates their efficiency as heating mediators and MRI contrast agents.

In the pursuit of optimized magnetic nanostructures for diagnostic and therapeutic applications, the role of nanoparticle architecture has been poorly investigated. In this study, we demonstrate that the internal collective organization of multi-core iron oxide nanoparticles can modulate their magnetic properties in such a way as to critically enhance their hyperthermic efficiency and their MRI T(1) and T(2) contrast effect. Multi-core nanoparticles composed of maghemite cores were synthesized through a polyol approach, and subsequent electrostatic colloidal sorting was used to fractionate the suspensions by size and hence magnetic properties.